The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI)
Bibliographic record
Abstract
OBJECTIVE: Our goal was to evaluate the association of APOE with amyloid deposition, cerebrospinal fluid levels (CSF) of Aβ, tau, and p-tau, brain atrophy, cognition and cognitive complaints in E-MCI patients and cognitively healthy older adults (HC) in the ADNI-2 cohort. METHODS: Two-hundred and nine E-MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated the impact of diagnostic status (E-MCI vs. HC) and APOE ε4 status (ε4 positive vs. ε4 negative) on cortical amyloid deposition (AV-45/Florbetapir SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based morphometry and Freesurfer version 5.1), CSF levels of Aβ, tau, and p-tau, and cognitive performance and complaints. RESULTS: E-MCI participants showed significantly impaired cognition, higher levels of cognitive complaints, greater levels of tau and p-tau, and subcortical and cortical atrophy relative to HC participants (p < 0.05). Cortical amyloid deposition and CSF levels of Aβ were significantly associated with APOE ε4 status but not E-MCI diagnosis, with ε4 positive participants showing more amyloid deposition and lower levels of CSF Aβ than ε4 negative participants. Other effects of APOE ε4 status on cognition and CSF tau levels were also observed. CONCLUSIONS: APOE ε4 status is associated with amyloid accumulation and lower CSF Aβ, as well as increased CSF tau levels in early prodromal stages of AD (E-MCI) and HC. Alternatively, neurodegeneration, cognitive impairment, and increased complaints are primarily associated with a diagnosis of E-MCI. These findings underscore the importance of considering APOE genotype when evaluating biomarkers in early stages of disease.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".